
Progress in Genomic Medicine
From Research to Clinical Application
- 1st Edition - November 4, 2021
- Author: Moyra Smith
- Language: English
- Paperback ISBN:9 7 8 - 0 - 3 2 3 - 9 1 5 4 7 - 2
- eBook ISBN:9 7 8 - 0 - 3 2 3 - 9 1 5 4 8 - 9
Progress in Genomic Medicine: From Research to Clinical Application provides a careful synthesis of the foundations, current trends and translational challenges in genomic m… Read more

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Request a sales quoteProgress in Genomic Medicine: From Research to Clinical Application provides a careful synthesis of the foundations, current trends and translational challenges in genomic medicine, clarifying pathways forward and enabling genomic medicine research and implementation across clinical settings and treatment development. Sections address the history and growth of genetic medicine, with a discussion of key studies in syndrome delineations, inherited diseases, biochemical genetics, and chromosome abnormalities, overview clinical applications made possible through genomic advances, with chapters on DNA sequencing for clinical genetic diagnosis, genotype-phenotype correlations in individuals and across populations, new-born screening for treatable genetic disorders, and more.
In addition, social, ethical and public health aspects of applying genomic technologies are included throughout. Here, Dr. Smith applies her experience and participation in the field, across its major milestones, to put current research, clinical advances, and ongoing questions in context.
- Traces the development of the field of genomic medicine, exploring key scientific advances and recent steps forward in clinical translation
- Considers the influence of genomic medicine on complex and monogenic pathology analysis, treatment plans and therapeutics
- Ties recent research and clinical advances to their historical context
Clinical Genomicists, Molecular Pathologists, Molecular Geneticists, Clinical Cytogeneticists, Clinical Geneticists, Primary Care Physicians (including Oncologists, Pediatricians, Neurologists, Cardiologists, and Neonatologists), and Genetic Counselors. Bioinformaticians, clinical informaticians, molecular laboratory technologists, and molecular pathology/molecular genetics trainees
- Cover image
- Title page
- Table of Contents
- Copyright
- Dedication
- Preface
- Acknowledgments
- Epigraph
- Part I: History and Growth of Genetic Medicine
- Chapter 1. Documentation of units of inheritance and their contribution to phenotype
- Abstract
- 1.1 Rediscovery of the laws of Mendel
- 1.2 Genes and genetics
- 1.3 Nucleic acids
- 1.4 The structure of DNA
- 1.5 DNA and chromatin
- 1.6 Applications of studies of chromosomes, genomes, genes, and gene expression to clinical medicine
- 1.7 Long-read sequencing for detection of genomic variants including structural chromosome abnormalities
- 1.8 Determination of the significance of structural variants in the genome
- 1.9 Mosaicism
- 1.10 Germline mutations
- 1.11 Genetic mosaicism in inborn errors of immunity
- References
- Further reading
- Chapter 2. Early documentation of inherited disorders through family studies
- Abstract
- 2.1 The Treasury of Human Inheritance
- 2.2 Ectrodactyly
- 2.3 Deafness
- 2.4 Hemophilia
- 2.5 Achondroplasia
- 2.6 Color blindness
- 2.7 Blue sclerotics and fragility of bone
- 2.8 Hereditary optic atrophy (Leber’s disease)
- 2.9 Huntington’s chorea
- 2.10 Duchenne muscular dystrophy
- 2.11 Determination of genetic causes of specific diseases and family studies
- References
- Further reading
- Chapter 3. Discoveries in physiology, biochemistry, protein, and enzyme studies between 1920 and 1970
- Abstract
- References
- Further reading
- Chapter 4. Early translation of biochemical, metabolic, and genetic discoveries into clinical medicine
- Abstract
- 4.1 ABO
- 4.2 Further information on the ABO blood group system
- 4.3 Secretor status
- 4.4 Mapping of the ABO locus to a chromosome
- 4.5 Rh blood group system
- 4.6 RHD genotyping
- 4.7 Chemical analyses and metabolism incorporating information gathered across the decades
- References
- Further reading
- Chapter 5. Advances in methods of genome analyses, nucleotide analyses, and implications of variants
- Abstract
- 5.1 Introduction
- 5.2 DNA sequencing
- 5.3 Applications of long-read sequencing
- 5.4 Sequence variant interpretation
- 5.5 Additional evidence for digenic or complex inheritance
- 5.6 Variants in nonprotein coding genomic regions
- 5.7 Haplotype phasing
- 5.8 Haplotype analysis
- 5.9 Long-range sequencing and identification of structural genomic variants leading to disease
- 5.10 Investigations of chromatin structure and genomic function
- 5.11 Methylation analyses
- 5.12 Imprinted genomic regions
- 5.13 Genetic disorders where analysis of methylation is important
- References
- Part II: Clinical Applications of Genomic Medicine
- Chapter 6. Expansion of use of genome analyses and sequencing in diagnosis of genetic diseases
- Abstract
- 6.1 Measurement toolkit for assessing the clinical utility of whole genome sequencing
- 6.2 One phenotype many genes
- 6.3 Genome sequencing in pediatric developmental defects
- 6.4 Optical DNA mapping in human genome studies
- 6.5 Transcriptome sequencing
- 6.6 Imprinting
- 6.7 Imprinting disorders
- 6.8 Prader−Willi syndrome and Angelman syndrome
- 6.9 Silver−Russell syndrome
- 6.10 GNAS locus
- 6.11 Epivariations
- 6.12 Multilocus imprinting disorders
- 6.13 Chromosomes genomes and sequence
- 6.14 Structural genomic variants
- 6.15 Assessment of copy number changes in different conditions and at different life stages
- 6.16 Prenatal exome sequence analysis
- 6.17 Deciphering Developmental Disorders Study
- 6.18 Investigations of causes of recurrent miscarriage
- 6.19 Sequencing in prenatal diagnosis: noninvasive prenatal testing
- References
- Further reading
- Chapter 7. Improved analyses of regulatory genome, transcriptome and gene function, mutation penetrance, and clinical applications
- Abstract
- 7.1 Introduction
- 7.2 Regulatory genome, gene expression, phenotype, and variability
- 7.3 Epigenetic factors relevant to gene expression
- 7.4 Regulatory circuit: Epimap
- 7.5 Genotype phenotype axis
- 7.6 Promoters
- 7.7 Transcription initiation and promoters
- 7.8 Transcription factors
- 7.9 Transcription termination
- 7.10 Polyadenylation
- 7.11 Alternate polyadenylation
- 7.12 The spliceosome
- 7.13 MicroRNAs and posttranscriptional regulation
- 7.14 Translation, ribosomes biogenesis, functions, and defects
- 7.15 Translation of mRNA to proteins and associated defects leading to disease
- 7.16 tRNAs
- 7.17 RNA surveillance
- 7.18 Translation
- 7.19 Nonsense-mediated decay
- 7.20 Nonsense mutations and human disease
- 7.21 Approved RNA targeted therapeutics
- 7.22 Therapy with short inhibitory RNAs
- 7.23 MicroRNAs in therapeutic use
- 7.24 RNA sequencing in diagnosis of genetic diseases
- 7.25 Penetrance of mutations and modified penetrance
- 7.26 Variable penetrance of disease due to polymorphisms in regulatory factors
- 7.27 Penetrance in inherited eye diseases
- 7.28 Primary immunodeficiency and incomplete penetrance
- References
- Chapter 8. Standardized phenotype documentation, documentation of genotype phenotype correlations
- Abstract
- 8.1 Phenotype and clinical genetics
- 8.2 Congenital malformations and syndromes
- 8.3 Variable phenotypes associated with specific mitochondrial mutations
- 8.4 Variable genomic abnormalities in individuals with the same phenotype
- 8.5 Standardized phenotype documentation, documentation of genotype phenotype correlations databases
- 8.6 Phenome-wide association studies
- 8.7 Dysmorphology syndromes with overlapping features due to defect in gene products that function in a specific pathway
- 8.8 Phenotypic defects due to defects in sonic hedgehog signaling pathway
- 8.9 Fibroblast growth factor signaling pathway
- 8.10 Fibroblast growth factor receptor defects
- 8.11 Transforming growth factor beta signaling pathway
- 8.12 Marfan syndrome 15q21.1 FBN1
- 8.13 FBN1 mutations, pathogenic, likely pathogenic, Marfan syndrome multiple submitters, without conflicts identified in Clin Var searches
- 8.14 Connective tissue disorder Ehlers−Danlos syndrome disorders
- 8.15 DNA methylation episignatures and phenotypic correlations
- References
- Chapter 9. Expansion of methods of gene editing therapy and analysis of safety and efficacy
- Abstract
- 9.1 Introduction
- 9.2 Therapies designed to block nucleotides or RNA derived from a specific gene
- 9.3 Oligonucleotide therapies
- 9.4 Delivery challenges in oligonucleotide therapies
- 9.5 Splice mutations and diseases
- 9.6 Antisense therapies under investigation
- 9.7 Genomic data leading to therapeutics
- 9.8 Pluripotent stem cells for investigation of disease manifestations and effects of therapies
- 9.9 Gene therapy by adding genes
- 9.10 Gene therapy
- 9.11 Stem cells and importance in gene therapy
- 9.12 Gene editing
- 9.13 Delivery of reagents for editing
- 9.14 Preclinical and clinical trials
- 9.15 NIH (National Institutes of Health) somatic cell gene editing program
- 9.16 Base editing
- 9.17 Programmable base editing
- 9.18 Prime editing
- 9.19 CRISPR-Cas theta
- 9.20 RNA editing
- 9.21 Gene therapy in specific diseases
- 9.22 Molecular analyses and therapies relevant to hearing loss
- 9.23 Therapy of cystic fibrosis including genetic approaches
- References
- Further reading
- Chapter 10. Public health applications of genetics including newborn screening and documentation of gene environment interactions
- Abstract
- 10.1 Recessive disorders carrier screening in specific populations
- 10.2 Newborn screening and hemoglobinopathies
- 10.3 Cystic fibrosis
- 10.4 Molecular-based therapeutics
- 10.5 Newborn screening, United States
- 10.6 Methods
- 10.7 Newborn screening in other parts of the world
- 10.8 Expanded carrier screening
- 10.9 Genetic disorders with high frequency in certain populations
- 10.10 Genetic disorders with increased frequency in other specific populations
- 10.11 Porphyrias
- 10.12 Factor V Leiden
- 10.13 Population-wide screening of adults
- 10.14 Hemochromatosis
- 10.15 Other disorders that illustrate the impact of gene environment interactions
- 10.16 Human genetic variation and pathogen sensitivity
- 10.17 Genetic and environmental factors and additional aspects of population screening
- References
- Further reading
- Chapter 11. Analysis of variants associated with abnormal drug responses, genetics, and genomics in drug design
- Abstract
- 11.1 Pharmacokinetics and pharmacodynamics
- 11.2 Biotransformation of medicinal compounds
- 11.3 World-wide distribution of genetic polymorphisms in the CYP450 system
- 11.4 Other factors and processes involved in biotransformation of drugs
- 11.5 Drug responses, variants, genetic and environmental factors
- 11.6 Gene variants that are disease causing and are also associated with abnormal drug reactions
- 11.7 Porphyrias
- 11.8 Identifying therapeutic targets and developing therapies
- 11.9 Translation of biomedical observations to treatments and health improvements
- 11.10 Fragment-based drug discovery
- 11.11 Monoclonal antibodies as therapeutic agents
- 11.12 Approaches to target identification and therapeutic design in specific genetic disorders
- 11.13 Inborn errors of metabolism
- 11.14 Lysosomal storage diseases and enzyme replacement therapy
- 11.15 Ceroid lipofuscinoses
- 11.16 Aminoacidopathies and organic acidemias
- 11.17 Transporter defects
- 11.18 Complexities of mitochondrial diseases and explorations of treatments
- 11.19 New approaches to cancer therapy
- References
- Further reading
- Chapter 12. Genetic and genomic medicine relevance to cancer prevention, diagnosis, and treatment
- Abstract
- 12.1 Introduction
- 12.2 Genes with germline mutations predisposing to cancer listed in order of frequency
- 12.3 Gene products with germline mutations that can lead to cancer and function of these products
- 12.4 Specific syndromes that include the presence of tumors
- 12.5 Retinoblastoma and RB1
- 12.6 Germline succinate dehydrogenase gene mutations and cancer predisposition
- 12.7 Hereditary gastrointestinal cancers
- 12.8 Germline mutations and developmental origins of cancer
- 12.9 Osteosarcoma
- 12.10 Genetic alterations in cancers in children, adolescents, and young adults
- 12.11 Adult cancers, driver gene mutations, and passenger gene mutations
- 12.12 DNA damage and repair
- 12.13 Lymphomas and leukemia
- 12.14 Myeloid leukemia
- 12.15 Providing insight into cancer-inducing mechanisms
- 12.16 Genome sequencing in cancer
- 12.17 Cell-free DNA analyses in testing for tumors
- 12.18 Cell-free studies including transcriptome analyses
- 12.19 Somatic mutations in cancer
- 12.20 Breast cancer risk genes
- 12.21 Whole genome sequencing of metastatic solid tumors
- 12.22 Therapy-related genetic and genomic information: molecular profiling and cancer therapies
- 12.23 Synthetic lethality
- 12.24 Cancer immunotherapy
- 12.25 CAR-T cells
- References
- Chapter 13. Benefits of the incorporation of genomic medicine in clinical practice
- Abstract
- 13.1 Genetic and genomic studies in congenital anomalies and/or neurodevelopmental anomalies
- 13.2 Rare disease medicine
- 13.3 Carrier screening
- 13.4 Diagnoses and management in disorders with phenotypic abnormalities
- 13.5 Databases of importance in searching for gene, genotype phenotype correlations
- 13.6 Genomic studies to guide diagnosis and therapy in epilepsy
- 13.7 Diagnostic testing for inborn errors of metabolism leading to seizures
- 13.8 Epilepsies, genetics, mechanisms, and therapy
- 13.9 Epilepsy genetics, genomics, and relevance to therapy
- 13.10 Common epilepsies
- 13.11 Cerebral palsy and genetic factors
- 13.12 Typical cerebral palsy
- 13.13 Monoamine neurotransmitter disorders
- 13.14 Spastic paraplegias and ataxias
- 13.15 Friedreich ataxia (FRDA)
- 13.16 Polyglutamine cerebellar ataxias
- 13.17 Autosomal recessive ataxias
- 13.18 Spinocerebellar ataxias
- 13.19 Spinocerebellar ataxias
- 13.20 Genomic medicine in common diseases in adults
- 13.21 Polygenic factors leading to hypertension
- 13.22 Coronary heart disease
- 13.23 Genetic-guided therapies
- 13.24 Approaches to determining polygenic risk scores
- 13.25 Familial hypercholesterolemia
- 13.26 Undiagnosed diseases and application of genetic and genomic studies
- References
- Further reading
- Chapter 14. Using insights from genomics to increase possibilities for treatment of genetic diseases
- Abstract
- 14.1 Introduction
- 14.2 Therapy lysosomal diseases
- 14.3 Neuroimmune disorders, autophagy lysosomes, and treatment
- 14.4 Mucopolysaccharidosis II (Hunter syndrome)
- 14.5 Strategies designed to increase the half-life of enzymes used in enzyme replacement strategies being considered in therapy
- 14.6 Gene-directed treatments
- 14.7 Hemoglobinopathy treatment including gene therapy
- 14.8 Gene-directed therapies in clinical trials in hemoglobinopathies
- 14.9 Hemoglobinopathy treatment through genetic silencing of BCL11A expression using antisense strategy
- 14.10 Splice mutations and diseases
- 14.11 Pluripotent stem cells in investigations of disease therapies
- 14.12 Relevance to protein folding and secondary modifications
- 14.13 Defects in ossification and mineralization
- 14.14 Osteogenesis imperfecta treatment
- 14.15 Ongoing clinical trials related to cell and gene therapy
- 14.16 Coagulation disorders
- 14.17 Von Willebrand factor and disease
- 14.18 Platelet receptors for Von Willebrand factor
- 14.19 Understanding mechanisms of rare diseases that may lead to therapy
- 14.20 Trinucleotide repeat disorders: progress toward therapy
- 14.21 Toward Huntington disease therapy
- 14.22 Protein clearance
- 14.23 Polyglutamine cerebellar ataxias
- 14.24 Duchenne muscular dystrophy
- 14.25 DMD therapy molecular approaches
- 14.26 Utrophin
- 14.27 Spinal muscular atrophy (autosomal recessive proximal muscular atrophy)
- 14.28 Antisense oligonucleotides in neurodegenerative diseases
- 14.29 Dynamic mutability of microsatellite repeats
- 14.30 Ocular gene therapy
- References
- Further reading
- Index
- No. of pages: 396
- Language: English
- Edition: 1
- Published: November 4, 2021
- Imprint: Academic Press
- Paperback ISBN: 9780323915472
- eBook ISBN: 9780323915489
MS
Moyra Smith
Dr. Moyra Smith is a Professor Emerita in the Department of Pediatrics and Human Genetics, College of Health Sciences, at the University of California, Irvine, and in past years has held appointments at the National Institutes of Health and Johns Hopkins University. In 2017, the UCI Emeriti Association awarded Dr. Smith the UCI Outstanding Emerita Award in recognition of her continuing research on genetics and genomics, strong record of publications, active engagement with programs in the Department of Pediatrics, mentoring of graduate students, and involvement with the CART Autism Center at UCI. Dr. Moyra Smith has published more than 100 scientific articles in peer-reviewed journals such as Frontiers in Molecular Biosciences, Molecular Psychiatry, the Journal of Medical Genetics (JMG), and Cytogenetics Cell Genetics.